Disrupted cognitive development following pediatric acquired demyelinating syndromes: a longitudinal study

ABSTRACT

Long-term cognitive deficits have been observed in some children who experience an acquired demyelinating syndrome (ADS). We examined changes in cognitive functioning over the first two years following incident ADS andtested whether normalized brain and thalamic volume accounted for decline over time. Twenty-five youth (mean age 12.8 years) with ADS, 9 of whom were diagnosed with multiple sclerosis (MS) and 16 of whom experienced monophasic ADS (monoADS), underwent two neuropsychological evaluationsand MRI scans at approximately6- and 24-months post ADS-onset. We examined changes in cognitive outcomes over time and between patient groups. Generalized linear mixed-effect regression models were used to examine the association of normalized brain and thalamic volumesbetween the two timepointswith cognitive z-scores. Cognitive performance was within the age-expected range for both groups and remained stable over time on 15 measures. In the combined sample of monoADS and MS patients, declines (p < .05) were noted on the Symbol Digit Modalities Test (SDMT), the Auditory Working Memory (AWM), and the WJ-III Visual Matching (VisMat)tests, but did not survive FDR correction. Clinically significant declines, as measured by the Reliable Change Index, were observed on the SDMT,AWM, and VisMattests by 19, 42, and 32%, respectively. Lower normalized brain volume at 6-months predicted a negative change in SDMT (B = 0.45, 95%CI: 0.07,0.83) and AWM (B = 0.30, 95%CI: 0.13, 0.47). Chronicity of demyelination is not required for cognitive decline nor for reduced brain volume, suggesting that even a single demyelinating event may negatively impact cognitive potential in children.

KEYWORDS:

• Multiple sclerosis
• monophasic acquired demyelinating syndrome
• longitudinal
• cognition
• development

Disclosure statement

No potential conflict of interest was reported by E. De Somma. Dr. Brown is the CEO of ShadowLab Research Inc., which provides consulting and research services to academic and pharmaceutical clients. Dr. Brooks receives royalties for the sales of the Pediatric Forensic Neuropsychology textbook (2012, Oxford University Press) and three pediatric neuropsychological tests [Child and Adolescent Memory Profile (ChAMP, Sherman and Brooks, 2015, PAR Inc.), Memory Validity Profile (MVP, Sherman and Brooks, 2015, PAR Inc.), and Multidimensional Everyday Memory Ratings for Youth (MEMRY, Sherman and Brooks, 2017, PAR Inc.)]. He is a co-author on the publically-available Parental Outcome Measure (Bemister et al., 2014). Dr. Narayanan has received research funding from the Canadian Institutes of Health Research, the International Progressive MS Alliance, the Myelin Repair Foundation and Immunotec. He has received honoraria/travel support from Genentech and MedDay, and personal compensation from NeuroRx Research. Dr. Marrie receives research funding from: CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC and the US Department of Defense, and is a co-investigator on studies receiving funding from Biogen Idec and Roche Canada. Dr. Bar-Or has participated as a speaker in meetings sponsored by and received consulting fees and/or grant support from: Accure, Atara Biotherapeutics, Biogen, BMS/Celgene/Receptos, GlaxoSmithKline, Gossamer, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech,Sanofi-Genzyme. Dr. Yeh has received research funding from NMSS, CMSC, CIHR, NIH, OIRM, SCN, CBMH Chase an Idea, SickKids Foundation, Rare Diseases Foundation, MS Scientific Foundation (Canada), McLaughlin Centre, Mario Battaglia Foundation. Investigator initiated research funding from Biogen. Scientific advisory: Biogen, Hoffman-LaRoche, Vielabio. Speaker honoraria: Saudi Epilepsy Society, NYU, MS-ATL; ACRS, PRIME. Dr. Banwell serves as a consultant to Novartis, Roche and UCB, and has received grant support from the Canadian Multiple Sclerosis Society and Foundation, National Multiple Sclerosis Society, and the National Institutes of Health..

Supplementary material

Supplemental data for this article can be accessed at https://doi.org/10.1080/09297049.2021.2002289.

Additional information

Funding

This work was supported by the Multiple Sclerosis Scientific Research Foundation [].